Phytomedicine最新文献

{"title":"Effect of Yiqi Fumai lyophilized injection on B-type natriuretic peptide levels in patients with acute decompensated ischemic heart failure: a multicenter, open-label, blinded-outcome, randomized controlled trial.","authors":"Xianliang Wang, Zhiqiang Zhao, Jingyuan Mao, Yue Deng, Zhongyong Liu, Xiaolong Wang, Yingqiang Zhao, Xiaohua Dai, Yonggang Wang, Ruyu Yuan, Chengliang Zhong, Huimin Fan, Ping Xie, Tinghai Du, Hong Zhang, Xiaofeng Wang, Yong Xu, Tianfu Niu, Qiwei Tang, Guanyu Wang, Shuzhong Shang, Xingsheng Zhao, Xulong Yan, Pu Xia, Chaofeng Liu, Bing Deng, Liyue Wang, Huanlin Wu, Bo Dong, Hong Yu, Meisheng Zheng, Zhentao Wang, Guoliang Zhao, Xin Li, Aliman Mahemuti, Zhiming Li, Hongxu Liu, Junqiang Yang, Mingjun Zhao, Ruihong Fan, E Tang, Guoyuan Zhao, Shuai Wang, Zhou Zhou, Jian Zhang, Boli Zhang","doi":"10.1016/j.phymed.2026.158191","DOIUrl":"10.1016/j.phymed.2026.158191","url":null,"abstract":"<p><strong>Background: </strong>Patients with acute decompensated ischemic heart failure (ADIHF) often present with severe clinical symptoms and poor quality of life. In China, Yiqi Fumai lyophilized injection (YQFM) is widely used in the treatment of ADIHF. However, high-quality evidence is still needed to support its efficacy and safety.</p><p><strong>Purpose: </strong>This study aims to assess the therapeutic efficacy and safety of YQFM in patients with ADIHF.</p><p><strong>Study design and methods: </strong>By conducting a multicenter, open-label, blinded-outcome, randomized controlled trial, we recruited patients with ADIHF from 37 hospitals in 20 regions of China from October 2015 to October 2018. Patients were allocated in a 1:1 ratio to either the YQFM group or the control group. Both groups received guideline-directed medical therapy (GDMT), with the YQFM group additionally receiving YQFM for 7 days. The primary outcome included the proportion of patients with a decrease from baseline B-type natriuretic peptide (BNP) value ≥ 30% on day 8 post-randomization. We evaluated the left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, Minnesota Living with Heart Failure Questionnaire (MLHFQ) score, and composite endpoints.</p><p><strong>Results: </strong>A total of 666 patients with ADIHF (332 in the YQFM group and 334 in the control group) were enrolled. The full analysis set (FAS) analysis revealed that the proportion of patients in the YQFM group with a reduction of at least 30% in BNP value on day 8 was higher than that in the control group (175 [55.21%] vs. 135 [41.93%], one-sided p < 0.001, two-sided p < 0.001; RR, 1.32 [95% CI, 1.12-1.56]). The YQFM group showed statistically significant improvements in LVEF, NYHA functional class, and MLHFQ scores compared to controls. There was no statistically significant difference between the two groups regarding composite endpoint events and adverse events during the follow-up period.</p><p><strong>Conclusions: </strong>Based on GDMT, the combined use of YQFM was associated with further reductions in BNP levels, improve quality of life and cardiac function in patients with ADIHF, without increasing safety risks. However, no significant differences were observed in clinical events, such as mortality or hospitalization, during the follow-up period.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"155 ","pages":"158191"},"PeriodicalIF":8.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spermidine alleviates sepsis-induced cardiomyopathy by improving mitochondrial quality and quantity via a Metallothionein 1-dependent antioxidant pathway.","authors":"Shiyun Long, Jiaxin Sun, Yaguang Wu, Jia Yi, Shuang Ren, Xiaoping Ran, Xiaofeng Li, Gautam Sethi, Zhenchun Luo, Chenyang Duan","doi":"10.1016/j.phymed.2026.158174","DOIUrl":"10.1016/j.phymed.2026.158174","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-induced cardiomyopathy (SICM) is characterized by mitochondrial dysfunction, impaired mitophagic flux, and overwhelming oxidative stress. Spermidine (SPD), a natural polyamine known to enhance autophagy and preserve cardiac function in aging and metabolic disorders, has not been systematically evaluated in the context of septic cardiomyopathy.</p><p><strong>Purpose: </strong>To determine the therapeutic potential and mechanistic basis of SPD in septic cardiac dysfunction.</p><p><strong>Methods: </strong>Network pharmacology, RNA sequencing, a cecal ligation and puncture (CLP) mouse model, and multiple cellular assays were integrated to assess the protective actions of SPD. Mitochondrial function, mitophagy flux, and oxidative stress were evaluated using transmission electron microscopy (TEM), immunohistochemistry (IHC), Western blotting, structured illumination microscopy (SIM), mitochondrial membrane potential assays, oxygen consumption rate (OCR) analysis, and mitochondrial DNA (mtDNA) quantification. Transcriptomic clustering and pathway enrichment identified molecular targets, which were validated through siRNA-mediated gene silencing.</p><p><strong>Results: </strong>SPD markedly attenuated SICM in vivo and in vitro by improving both mitochondrial quantity and quality. It restored sepsis-impaired mitophagy by upregulating LC3B and ATG7, promoting autophagosome maturation, and enhancing cellular ubiquitination. Transcriptomic profiling highlighted metallothionein-1 (MT1) as a key node in metal-ion response pathways. SPD activated the NRF2-MT1-SOD2 antioxidant axis, reduced mitochondrial reactive oxygen species (mtROS) under lipopolysaccharide (LPS) stimulation, and reversed sepsis-induced suppression of SOD2. MT1 knockdown abolished SPD-mediated SOD2 stabilization and mtROS clearance, confirming its essential role in SPD's cardioprotective effects.</p><p><strong>Conclusion: </strong>SPD mitigates SICM by orchestrating the restoration of mitochondrial quality control, normalization of mitophagic flux, and stabilization of cellular redox homeostasis. These findings support SPD as a promising therapeutic candidate for septic cardiomyopathy.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"155 ","pages":"158174"},"PeriodicalIF":8.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147778962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating natural bioactive chronobiotics in a C. elegans circadian disruption system induced by light-temperature entrainment.","authors":"Yiwen Guo, Tao Zhang, Ying Xu, Ming Chang, Ruijie Liu","doi":"10.1016/j.phymed.2026.158129","DOIUrl":"10.1016/j.phymed.2026.158129","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of circadian rhythm disruption (CRD) is increasing due to the worsening light pollution, rising societal stress, and globalized lifestyles. Long-term CRD can cause significant physiological changes and raise the risk of various health disorders. Natural bioactive compounds (NBC) are showing promise as novel circadian modulators because they can precisely target core clock networks, be administered flexibly, and have multi-target effects, requiring efficient screening models.</p><p><strong>Purpose: </strong>The objective of this study was to establish and characterize a CRD model in C. elegans and to explore its applicability for evaluating the chronobiotic potential of NBCs.</p><p><strong>Methods: </strong>A synchronized light-temperature perturbation protocol was used to induce a stable CRD state in C. elegans. The model's validity was rigorously assessed by monitoring locomotor behavioral rhythms and quantifying transcriptional changes in core clock genes. Rhythm integrity and periodicity were analyzed using the Biodare2 platform. The restorative effects of administered nine NBCs were evaluated through this integrated behavioral, physiological, and molecular framework.</p><p><strong>Results: </strong>The environmental perturbation successfully recapitulated key features of human CRD, leading to markedly disturbed behavioral rhythms and altered expression of core clock genes. The model showed good reproducibility and proved suitable for compound evaluation. Several chronobiotic compounds, including nobiletin, serotonin, N-acetylserotonin, melatonin, catechin, and capsaicin, alleviated CRD-associated phenotypes to varying degrees, demonstrating the model's utility for investigating the circadian regulatory effects of NBCs.</p><p><strong>Conclusion: </strong>Our multidimensional analysis in C. elegans reveals that natural bioactive compounds can modulate CRD, offering new perspectives on the therapeutic potential of plant-derived chronobiotics.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"155 ","pages":"158129"},"PeriodicalIF":8.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current advances in restoring intestinal barrier homeostasis by natural medicines.","authors":"Yihan Wang, Sheng Tan, Jie Huang, Qibiao Wu, Xiaoyan Shen, Weilian Bao","doi":"10.1016/j.phymed.2026.158144","DOIUrl":"10.1016/j.phymed.2026.158144","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The intestinal mucosa serves as a critical interface separating the internal environment of the human body from the external milieu, with its barrier function determining the appropriate entry of luminal contents. Dysfunction of this barrier is closely associated with the development of intestinal disorders, such as inflammatory bowel disease and irritable bowel syndrome, as well as a spectrum of extraintestinal diseases. Both Eastern and Western traditional medicine regard the intestine as central to overall health, and since most natural medicines are administered orally, they are likely to interact with the intestinal mucosa and could potentially influence intestinal barrier homeostasis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;This review summarizes the mechanisms by which natural medicine (including compounds and extracts) restores the homeostasis of the intestinal barrier, and further elucidates their therapeutic implications for ameliorating both local intestinal pathologies and systemic extraintestinal diseases.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This review is based on a comprehensive synthesis of recent literature regarding the restoration of intestinal barrier homeostasis. The focus is on the mechanisms through which natural medicines, including herbal extracts and traditional Chinese medicine (TCM) formulations, influence intestinal epithelial cells, immune regulation, and gut microbiota balance, as well as the role of the \"Gut-X axis\" in modulating extraintestinal diseases. Relevant studies published in English between January 1, 2020, and September 30, 2025, were identified through a systematic search of databases such as PubMed, Web of Science, Scopus, and Google Scholar. Only original preclinical research, including in vitro, ex vivo, and animal model studies, was considered. Keywords related to natural medicines, intestinal barrier integrity, TCM, herbal extracts, formulations, and relevant mechanisms (e.g., inflammation, microbiota regulation, epithelial integrity) were used for the search. Studies were assessed for relevance, and key data on therapeutic effects and mechanisms were extracted for further analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The analysis demonstrates the multi-targeted efficacy of natural medicines in restoring intestinal barrier homeostasis, specifically in: enhancing epithelial integrity; regulating intracellular programs such as apoptosis and autophagy; balancing immune responses; remodeling the gut microbiota-metabolite profile; and exerting therapeutic impact across established \"Gut-X axes\" (specifically the Gut-Lung, Gut-Liver, Gut-Brain, Gut-Endocrine, and Gut-Heart axes).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The multi-targeted nature of natural medicines mirrors the complexity of intestinal barrier regulation, yet also presents a challenge for mechanistic delineation. Overcoming the inherent limitations of current research necessitates a paradigm shift towards a systems medicine appr","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"155 ","pages":"158144"},"PeriodicalIF":8.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Echinacoside targets HSC70 to inhibit osteoclastogenesis and ameliorate ovariectomy-induced osteoporosis.","authors":"Dong Han, Qian-Tong Wu, Lei Wang, Jian-Guang Li, Ping Li, Fei Li","doi":"10.1016/j.phymed.2026.158176","DOIUrl":"10.1016/j.phymed.2026.158176","url":null,"abstract":"<p><strong>Background: </strong>Echinacoside (ECH), a natural phenylethanoid glycoside isolated from Cistanche deserticola, exhibits promising therapeutic potential against osteoporosis (OP). Nevertheless, its specific molecular targets and the mechanisms involved are not yet fully understood.</p><p><strong>Purpose: </strong>This study integrates small-molecule affinity chromatography with both RANKL-induced osteoclastogenesis and ovariectomy (OVX)-induced rat models of OP to systematically investigate the molecular targets and mechanisms responsible for the anti-OP effects of ECH.</p><p><strong>Methods: </strong>Small-molecule affinity chromatography and molecular dynamics simulations were employed to identify the direct molecular targets of ECH and their potential binding sites. Subsequently, combined with molecular biology techniques, the RANKL-induced osteoclastogenesis model was utilized to further elucidate the molecular mechanisms by which ECH regulates bone homeostasis. Finally, the anti-OP effect of ECH was confirmed in vivo using an OVX-induced rat models of OP.</p><p><strong>Results: </strong>This study reveals that heat shock cognate 71 kDa protein (HSC70) serves as a key cellular target of ECH in modulating osteoclastogenesis. The amino acids ARG36 and ARG272 of HSC70 are confirmed as the primary binding sites for ECH. Notably, HSC70 is markedly upregulated in both OP models and clinical patient samples. Mechanistically, ECH suppresses osteoclastogenesis by promoting ubiquitination-mediated degradation of IKKβ. Furthermore, knockdown of Hsc70 demonstrated a similar biological effect as ECH treatment. In vivo studies validate that ECH, via targeting HSC70, markedly ameliorates bone loss and metabolic dysregulation in the OVX-induced rat OP model. Specifically, Hsc70 overexpression induces bone loss in normal rats. Conversely, Hsc70 knockdown alleviates bone loss in OVX rats. Moreover, both overexpression and knockdown of Hsc70 abolish the therapeutic effect of ECH in OVX rats.</p><p><strong>Conclusion: </strong>This work reveals HSC70 as a novel regulator of bone remodeling and proposes ECH, a new HSC70 inhibitor, as a promising therapeutic agent. This study provides important insights into the pathogenesis of OP and proposes an innovative targeting strategy for metabolic bone disorders.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"155 ","pages":"158176"},"PeriodicalIF":8.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromones from Saposhnikovia divaricata modulate m⁶A RNA methylation-mediated macrophage polarization by targeting CBLL1 to ameliorate RA.","authors":"Xu Yang, Zhichao Hao, Shiqi Xu, Gangtao Bu, Min Wang, Yan Sun, Yuxin Li, Yiran Wang, Qingshan Chen, Lili Zhang, Haixue Kuang, Lili Huang, Yan Liu","doi":"10.1016/j.phymed.2026.158172","DOIUrl":"10.1016/j.phymed.2026.158172","url":null,"abstract":"<p><strong>Background: </strong>Over-activated M1 macrophages, which destroyed the balance of macrophage phenotype in the synovial microenvironment, play a pivotal role in rheumatoid arthritis (RA) progression. Increasing evidence indicates that m⁶A RNA methylation serves as a crucial epigenetic regulatory mechanism in modulating the transition from M0 to M1 macrophages. Saposhnikovia divaricata (Turcz.) Schischk treats RA through immune regulation. In our previous study, chromones (CHR) from Saposhnikovia divaricata could alleviate RA by inhibiting the pathological manifestations of synovial inflammation, but the mechanism of action remains to be elucidated.</p><p><strong>Purpose: </strong>To elucidate the pharmacology and mechanism of CHR on m⁶A RNA methylation mediated M1 macrophages for RA treatment.</p><p><strong>Methods: </strong>In CIA mice, joint inflammation was assessed clinically and histologically, while bone changes were quantified by micro-CT and H&E staining. In vitro, the effects of CHR on macrophage polarization were analyzed by examining cell surface proteins, effector cytokine secretion, and master transcription factor expression. Target determination was interrogated through dot blot combined with the GEO database, corroborated by the sgRNA of CBLL1. Downstream mechanistic pathway validation mainly included quantification of expression via RIP-qPCR, CETSA, and DARTS. A co-culture system of MH7A and polarized THP-1 cells was utilized to assess synovial inflammation.</p><p><strong>Results: </strong>CHR relieved paw swelling and joint damage and regulated macrophage polarization in CIA mice. Moreover, polarized macrophages were significantly repressed. CHR also modulated the expression of M1 macrophage-associated proteins to influence abnormal characteristics of synovial inflammation. Furthermore, CHR could directly bind to CBLL1 and inhibit its expression and function in macrophages. By knocking down CBLL1, CHR might be involved in regulating macrophage polarization by modulating CBLL1-mediated STAT1/NF-κB expression.</p><p><strong>Conclusion: </strong>CHR could inhibit M1 macrophage polarization by regulating CBLL1-mediated m⁶A RNA methylation to treat RA.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"155 ","pages":"158172"},"PeriodicalIF":8.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"GelMA@APPA Microspheres Promote Chondrocyte Regeneration and Alleviate Osteoarthritis via Fgfr2 Activation\" [2025 Feb:137:156176. doi: 10.1016/j.phymed.2024.156176/PHYMED-D-24-03041].","authors":"Jiakai Wang, Tao Sun, Rong Zhang, Tingting Wang, Yishuo Li","doi":"10.1016/j.phymed.2026.157897","DOIUrl":"10.1016/j.phymed.2026.157897","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"157897"},"PeriodicalIF":8.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primin inhibits New Delhi metallo-β-lactamase-5 and restores meropenem activity in Escherichia coli.","authors":"Gaoqiang Wei, Yaozu Yang, Chunhua Wang, Xiuying Zhang","doi":"10.1016/j.phymed.2026.158175","DOIUrl":"10.1016/j.phymed.2026.158175","url":null,"abstract":"<p><strong>Background: </strong>New Delhi metallo-β-lactamase-5 (NDM-5)-producing Escherichia coli is a major driver of carbapenem resistance, and clinically effective metallo-β-lactamase inhibitors remain unavailable. Primin (PRI), a benzoquinone isolated from Primula obconica, is a plant-derived compound with potential bioactivity. Because meropenem (MEM) is a clinically important carbapenem that is readily hydrolyzed by NDM-5, it was selected as the partner antibiotic to determine whether PRI could restore its antibacterial activity.</p><p><strong>Purpose: </strong>This study aimed to evaluate PRI as an NDM-5 inhibitor and to determine whether it could restore the activity of MEM.</p><p><strong>Methods: </strong>Structure-based virtual screening was performed against NDM-5 using the crystal structure (Protein Data Bank entry 4TZE) and a natural compound library. Enzymatic inhibition assays, minimum inhibitory concentration determination, checkerboard assays for fractional inhibitory concentration index calculation, and time-kill assays were conducted using an NDM-5-producing E coli strain. Bio-layer interferometry, molecular docking, molecular dynamics simulations with molecular mechanics Poisson-Boltzmann surface area analysis, and site-directed mutagenesis (Met67Ala and Phe70Ala) were applied to characterize binding interactions. A murine infection model was used to evaluate in vivo efficacy.</p><p><strong>Results: </strong>PRI inhibited NDM-5 activity in a dose-dependent manner (IC₅₀ = 16.8 ± 0.3 μM) and showed no significant antibacterial activity alone. In combination with MEM, PRI exhibited strong synergistic effects (fractional inhibitory concentration index = 0.125) and enhanced bactericidal activity. Binding analyses demonstrated that PRI interacts with the catalytic pocket of NDM-5, involving residues Met67 and Phe70. Mutations at these residues reduced binding affinity and inhibitory activity. In vivo, PRI combined with MEM reduced bacterial burden, attenuated inflammation, and alleviated tissue injury.</p><p><strong>Conclusions: </strong>PRI, a plant-derived benzoquinone, inhibits NDM-5 and restores MEM activity against Escherichia coli. These findings suggest that PRI is a promising lead compound for developing metallo-β-lactamase inhibitors and antibiotic adjuvants.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"155 ","pages":"158175"},"PeriodicalIF":8.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salvianolic acid B attenuates abdominal aortic aneurysm via inhibition of ferroptosis and inflammation.","authors":"Si-Jia Jin, En-Guang Dou, Lei Wang, Lian-Wen Qi, Feng Wei, Lei Zhang","doi":"10.1016/j.phymed.2026.158181","DOIUrl":"10.1016/j.phymed.2026.158181","url":null,"abstract":"<p><strong>Background: </strong>Abdominal aortic aneurysm (AAA) is a life-threatening vascular disorder characterized by progressive aortic wall degeneration, inflammation, and vascular smooth muscle cells (VSMCs) loss. Despite extensive research, no effective pharmacological treatment is currently available to prevent or halt AAA progression.</p><p><strong>Purpose: </strong>This study aimed to discover effective therapeutic agents for AAA and identify potential natural compounds with pharmacological efficacy against the disease by targeting matrix metalloproteinase-2 (MMP2), a key enzyme involved in extracellular matrix degradation and aneurysm progression.</p><p><strong>Methods: </strong>An integrated screening strategy combining cytotoxicity evaluation, high-content immunofluorescence imaging, and molecular docking was applied to an angiotensin II (Ang II)-stimulated rat aortic smooth muscle cells (RASMCs) model. A total of 138 natural products were systematically assessed. The anti-aneurysmal efficacy of the identified compound was further validated in both CaCl₂-induced and Ang II-infused ApoE^-/- mouse models of AAA. Network pharmacology and metabolomic analyses were performed to elucidate the underlying molecular mechanisms.</p><p><strong>Results: </strong>Salvianolic acid B (Sal B), a major polyphenol from Salvia miltiorrhiza, was identified as a potent anti‑AAA candidate. It suppressed aneurysm formation, reduced elastin degradation, and attenuated inflammatory infiltration in vivo, while preserving the contractile phenotype, lowering ROS, and inhibiting MMP activity in Ang II‑stimulated RASMCs in vitro. Mechanistically, Ang II suppresses NRF2, leading to downregulation of the System Xc⁻-GPX4 axis and promoting lipid peroxidation and VSMC ferroptosis. This ferroptosis then activates the AGE-RAGE pathway, amplifying inflammation and MMP‑driven matrix degradation. Sal B counteracts this cascade by restoring NRF2 activity, improving lipid metabolism, and inhibiting MMPs, thereby blocking ferroptosis‑initiated inflammation and preserving aortic integrity.</p><p><strong>Conclusion: </strong>Salvianolic acid B exerts protective effects against AAA by attenuating oxidative stress, ferroptosis, and inflammation. These findings highlight Sal B as a promising natural therapeutic candidate for the prevention and treatment of abdominal aortic aneurysm.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"155 ","pages":"158181"},"PeriodicalIF":8.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enterolactone mitigates atherosclerosis by facilitating resolution of ferroptosis-associated intimal inflammation via the Keap1/Nrf2/GPX4 pathway.","authors":"Shuhui Chai, Yihang Zhang, Yi Guo, Danli Cao, Jiaxing Wang, Yu Yan, Yuxue Shi, Zhiyi Yuan, Xiaoyu Wang, Tingting Tong, Ziyi Zhen, Yanhao Huo, Kaiwen Zhang, Fenglin Wang, Gui-Rong Liu, Weiheng Li, Xiaohui Xu, Tao Ban, Shu-Lin Liu, Huidi Liu","doi":"10.1016/j.phymed.2026.158178","DOIUrl":"10.1016/j.phymed.2026.158178","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis is the inflammatory consequence of lipid accumulation with plaque formation in the vascular intima and is a common condition to develop into various cardiovascular diseases. Current therapies do not always lead to satisfactory treatment outcomes. Enterolactone, a mammalian lignan produced by bacterial transformation from plant lignans, has a preventive effect against cardiovascular disease. However, its effect on atherosclerosis and the underlying mechanism of action remain unclear.</p><p><strong>Purpose: </strong>To explore the therapeutic effect of ENL on atherosclerosis and elucidate the underlying mechanism.</p><p><strong>Methods: </strong>We established a model of atherosclerosis on ApoE-/- C57BL/6 mice by high fat diet. The aortic root was collected and sectioned to assess arterial plaque area, collagen fibrillar proliferation, and lipid content. RT-qPCR was used to determine the inflammatory response in the artery of mice. The serum from mice was isolated to measure lipid levels, and the fecal microbiota was analyzed by 16S rDNA. H₂O₂ was used to induce HUVEC injury and ferroptosis to mimic endothelial cell dysfunction in atherosclerosis, and the inhibitory effect of ENL on HUVEC ferroptosis was appraised by monitoring ferroptosis indexes and levels of iron-related proteins.</p><p><strong>Results: </strong>In the animals, enterolactone significantly improved lipid metabolism, attenuated ferroptosis occurring in the intima, facilitated the antioxidant mechanisms, and promoted healing of the endothelial lesions, by interacting with Nrf2. Of great importance, enterolactone massively altered the gut microbiota toward a curative outcome by elevating the abundance of beneficial bacteria, such as the SCFA-producing taxa. Additionally, ENL suppresses lipid peroxidation and inflammatory activation in HUVECs by regulating the Keap1/Nrf2/GPX4 pathway, and knocking down Nrf2 attenuates the treatment effect of ENL.</p><p><strong>Conclusion: </strong>Enterolactone effectively resolves intimal inflammation and redresses atherosclerosis by ameliorating the gut microbiome and modulating lipid metabolism via the Keap1/Nrf2/GPX4 pathway.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"155 ","pages":"158178"},"PeriodicalIF":8.3,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}